A Family With Corticobasal Degeneration, Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Dementia (P3.085)

OBJECTIVE: To describe clinical, PET, pathological, and genetic findings of an extensive kindred with hereditary corticobasal degeneration (CBD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and dementia. DESIGN/METHODS: Two family members including the index case were examined neurologically. Clinical information of the other family members was collected from questionnaires. Three asymptomatic family members underwent PET. Proband was examined postmortem. Genetic studies were performed. RESULTS: Pedigree contains 64 individuals with 8 affected patients. The inheritance is likely autosomal dominant with reduced penetrance. The index case developed progressive speech and language difficulties at the age of 64 years. On examination at the age of 68 years, she showed non-fluent aphasia, word-finding difficulties, circumlocution, frontal release signs, and right-sided bradykinesia, rigidity, and pyramidal signs. She died 5 years after the symptomatic disease onset. The neuropathology was characterized by numerous ballooned neurofilament-positive neurons, tau-positive astrocytic plaques, and oligodendroglial coiled bodies, all typical of CBD. Two other family members were diagnosed with Parkinsonism and behavioral problems, two with PD alone, one with ALS alone, one with dementia, and one with progressive gait and speech problem. PET scanning with DTBZ binding and FDG uptake on three asymptomatic family members was normal. Genetic sequencing on two symptomatic patients including proband excluded mutations in the MAPT gene. CONCLUSIONS: Such complex phenotypes rarely occur and, if at all, then are usually associated with MAPT mutations. However, in this family, MAPT mutations have been excluded, implicating another causative gene. We are conducting further genetic studies on this family. Study Supported By: P50NS72187; the Family of Carl Edward Bolch, Jr. and Susan Bass Bolch; the Max Kade Foundation. Disclosure: Dr. Fujioka has nothing to disclose. Dr. Sanchez Contreras has nothing to disclose. Dr. Strongosky has received personal compensation for activities with Novartis, Eisai Inc., and the ANS. Dr. Tacik has nothing to disclose. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Stoessl has received personal compensation for activities with Teva Neuroscience, AbbVie, and UCB Pharma. Dr. Baker has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant. Dr. Wszolek has received personal compensation in an editorial capacity for Parkinsonism and Related Disorders, and for the European Journal of Neurology. Dr. Wszolek has received license fee payments from Mayo Clinic. Dr. Wright has received research support from the National Institutes of Health, Mayo Clinic Florida, and the Dystonia Medical Research Foundation.